TY - JOUR
T1 - Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality
T2 - Meta-analysis of individual patient data for 8135 women in 22 randomised trials
AU - Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
AU - McGale, P.
AU - Taylor, C.
AU - Correa, C.
AU - Cutter, D.
AU - Duane, F.
AU - Ewertz, M.
AU - Gray, R.
AU - Mannu, G.
AU - Peto, R.
AU - Whelan, T.
AU - Wang, Y.
AU - Wang, Z.
AU - Darby, S.
AU - Albain, K.
AU - Anderson, S.
AU - Arriagada, R.
AU - Barlow, W.
AU - Bergh, J.
AU - Bergsten Nordström, E.
AU - Bliss, J.
AU - Burrett, J. A.
AU - Buyse, M.
AU - Cameron, D.
AU - Carrasco, E.
AU - Clarke, M.
AU - Coleman, R.
AU - Correa, C.
AU - Coates, A.
AU - Collins, R.
AU - Costantino, J.
AU - Cutter, D.
AU - Cuzick, J.
AU - Darby, S.
AU - Davidson, N.
AU - Davies, C.
AU - Davies, K.
AU - Delmestri, A.
AU - Di Leo, A.
AU - Dowsett, M.
AU - Elphinstone, P.
AU - Evans, V.
AU - Ewertz, M.
AU - Forbes, J.
AU - Gelber, R.
AU - Gettins, L.
AU - Geyer, C.
AU - Gianni, L.
AU - Gnant, M.
AU - Goldhirsch, A.
AU - Godwin, J.
N1 - Funding Information:
The main acknowledgments are to the thousands of women who took part in the trials, to the staff who treated and cared for them and who undertook the trials and shared their data with the Secretariat, and to the CTSU, which hosts this collaboration. EBCTCG is funded from the general long-term financial support from Cancer Research UK, the British Heart Foundation, and the UK Medical Research Council to the CTSU, University of Oxford. For a full list of EBCTCG collaborators, see appendix pp 86–89 .
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Background Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. Methods We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. Findings 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fl uorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). Interpretation After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.
AB - Background Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection. Methods We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status. Findings 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fl uorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04). Interpretation After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.
UR - http://www.scopus.com/inward/record.url?scp=84902807345&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(14)60488-8
DO - 10.1016/S0140-6736(14)60488-8
M3 - Article
C2 - 24656685
AN - SCOPUS:84902807345
SN - 0140-6736
VL - 383
SP - 2127
EP - 2135
JO - The Lancet
JF - The Lancet
IS - 9935
ER -